The Norwalk virus and related 27nm caliciviruses are the major cause of nonbacterial epidemic gastroenteritis that occurs in family, school, institutional, or community-wide outbreaks affecting adults, school-aged children, and some young children, as well. Epidemiologic studies of these viruses have been hampered by the inability to grow the human caliciviruses in cell culture. A molecular approach using recombinant proteins for the development of diagnostic assays has enabled large-scale epidemiologic studies that are defining the extent of antigenic diversity among the human caliciviruses and the role of this diversity in the natural history of these viruses.